Human aging continues to be an enigma, despite recent advances in medical and biochemical understanding of pathological processes in cells and tissues. A number of mechanisms have been proposed to explain aging processes. The most promising of these deal with deteriorative changes at the cellular, subcellular and molecular level. In the study proposed here we will investigate aging mechanisms in normal human diploid cells in culture. This system manifests a finite lifespan in vitro and is therefore a promising model for cellular aging. The long range objectives of this program are to identify molecular mechanisms for aging in cell systems and to test possible methods by which aging damage may be inhibited. To pursue these objectives we propose to examine the growth, morphology, composition and function of human diploid lung fibroblasts, WI-38, as related to their in vitro "age", or passage level, when grown under different environmental conditions. The unique feature of this program is the coordination of diverse talents within a single organization to study aging in cells and cell fractions produced by standard procedures in amounts commensurate with biochemical study. Central facilities will produce mitotic and postmitotic cells at various stages in their life span and after various environmental treatments. These treatments will be designed to test the hypothesis of aging by testing the effects of substances which accelerate or retard cell senescence. Cells and cell fractions will be available for use by the cooperating laboratories. The scope of the investigation will deal with six areas: 1. Cell Cultivation. 2. Damage Mechanisms - Membranes. 3. DNA and Protein Biosynthesis. 4. Accumulation of Damage. 5. Protection Against Damage. 6. Computer Applications. -- Research, resource and information flows will be coordinated to provide means for the exchange and dissemination of information.